NEFL

Summary

NEFL (neurofilament light chain, HGNC:7739) is a protein-coding gene on chromosome 8p21.2, encoding Neurofilament light polypeptide (P07196). Neurofilaments usually contain three intermediate filament proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of neuronal caliber.

Neurofilaments are type IV intermediate filament heteropolymers composed of light, medium, and heavy chains. Neurofilaments comprise the axoskeleton and they functionally maintain the neuronal caliber. They may also play a role in intracellular transport to axons and dendrites. This gene encodes the light chain neurofilament protein. Mutations in this gene cause Charcot-Marie-Tooth disease types 1F (CMT1F) and 2E (CMT2E), disorders of the peripheral nervous system that are characterized by distinct neuropathies. A pseudogene has been identified on chromosome Y.

Source: NCBI Gene 4747 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Charcot-Marie-Tooth disease type 2 (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 666 total — 30 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 106
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_006158

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7739
Approved symbol	NEFL
Name	neurofilament light chain
Location	8p21.2
Locus type	gene with protein product
Status	Approved
Aliases	NFL, CMT1F, CMT2E, NF68, PPP1R110
Ensembl gene	ENSG00000277586
Ensembl biotype	protein_coding
OMIM	162280
Entrez	4747

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000610854, ENST00000615973, ENST00000916556

RefSeq mRNA: 1 — MANE Select: NM_006158 NM_006158

CCDS: CCDS75712

Canonical transcript exons

ENST00000610854 — 4 exons

Exon	Start	End
ENSE00003713115	24954181	24954305
ENSE00003730059	24953476	24953795
ENSE00003731174	24950955	24952952
ENSE00003746083	24955472	24956612

Expression profiles

Bgee: expression breadth ubiquitous, 214 present calls, max score 99.97.

FANTOM5 (CAGE): breadth broad, TPM avg 40.6536 / max 2582.0070, expressed in 619 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92399	40.4950	619
92386	0.0631	12
92384	0.0494	23
92385	0.0460	11

Top tissues by expression

281 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
dorsal root ganglion	UBERON:0000044	99.97	gold quality
pons	UBERON:0000988	99.94	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.93	gold quality
endothelial cell	CL:0000115	99.91	gold quality
superior vestibular nucleus	UBERON:0007227	99.84	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.83	gold quality
orbitofrontal cortex	UBERON:0004167	99.76	gold quality
substantia nigra pars compacta	UBERON:0001965	99.73	gold quality
middle temporal gyrus	UBERON:0002771	99.71	gold quality
frontal pole	UBERON:0002795	99.69	gold quality
superior frontal gyrus	UBERON:0002661	99.55	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.52	gold quality
primary visual cortex	UBERON:0002436	99.32	gold quality
parietal lobe	UBERON:0001872	99.31	gold quality
occipital lobe	UBERON:0002021	99.30	gold quality
CA1 field of hippocampus	UBERON:0003881	99.30	gold quality
lateral globus pallidus	UBERON:0002476	99.29	gold quality
trigeminal ganglion	UBERON:0001675	99.24	gold quality
postcentral gyrus	UBERON:0002581	99.24	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.16	gold quality
Brodmann (1909) area 10	UBERON:0013541	99.16	gold quality
ventral tegmental area	UBERON:0002691	99.13	gold quality
medulla oblongata	UBERON:0001896	98.92	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.78	gold quality
frontal cortex	UBERON:0001870	98.68	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.60	gold quality
entorhinal cortex	UBERON:0002728	98.58	gold quality
prefrontal cortex	UBERON:0000451	98.55	gold quality
right frontal lobe	UBERON:0002810	98.17	gold quality
adult organism	UBERON:0007023	98.15	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	7146.23
E-MTAB-9154	yes	5793.27
E-HCAD-56	yes	4536.80
E-MTAB-6911	yes	4010.96
E-HCAD-25	yes	2989.61
E-MTAB-11121	yes	1012.89
E-HCAD-5	yes	916.01
E-GEOD-75140	yes	436.32
E-HCAD-35	yes	46.47
E-GEOD-93593	yes	8.78
E-ANND-3	yes	3.45
E-MTAB-7303	no	2786.66
E-HCAD-30	no	774.59

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, FOS, JUN, OPTN, SP1, TFAP2A

miRNA regulators (miRDB)

124 targeting NEFL, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-507	99.97	70.11	1915

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• To study if the increase of levels of neurofilament (NF)-M and NF-L in brain of Alzheimer’s diseases (AD) is caused by increase of NF-M and NF-L. (PMID:12133495)
• Mutational anlyses of NF-L gene in Parkinsonian patients revealed three silent DNA changes (G163A, C224T, C487T) in three unrelated patients. Association studies based on these haplotypes found no differences between PD patients and controls. (PMID:12231460)
• Eight novel sequence variations have been identified in the NF-L gene in patients with Charcot-Marie-Tooth phenotype: 5 variants are polymorphisms, including 3 single nucleotide polymorphisms (SNPs), and 3 other missense mutations have been detected. (PMID:12477167)
• Selective loss of trans-acting instability determinants of neurofilament L mRNA in amyotrophic lateral sclerosis spinal cord. (PMID:12730211)
• We report a family with a Pro22Ser mutation in the neurofilament-light gene (NF-L; CMT2E) manifesting electrophysiologically as the demyelinating type 1 CMT (CMT1) and pathologically as an axonopathy with giant axons and accumulation of disorganized NF (PMID:15111691)
• out of frame mutation does not result in Charcot-Marie-Tooth disease type 2E. (PMID:15654615)
• Interaction of NF-L with N-methyl-D-aspartate receptor (NMDAR) in a heterologous system causes increased cell surface expression of NMDARs, apparently effected by reduction in ubiquitination state of the NR1 subunit of NMDAR. (PMID:15686490)
• mutations in neurofilaments are possible risk factors that may contribute to pathogenesis in amyotrophic lateral sclerosis in conjunction with one or more additional genetic or environmental factors, but are not significant primary causes (PMID:16084104)
• The mechanism of massive aggregate formation of NF-L Charcot-Marie-Tooth disease mutants (P22S and P22T) is revealed, as well as the effect of phosphorylation at the head domain on aggregate alleviation. (PMID:16452125)
• Cerebrospinal fluid levels of neurofilament protein L are significantly increased in patients with multiple system atrophy predominated by parkinsonism. (PMID:16678934)
• This study suggests that this I214M substitution in the NEFL gene was not a direct cause of the disease but could be a polymorphism or possibly a modifier of the CMT phenotype. (PMID:16930284)
• A subgroup of FTD patients had remarkably high CSF levels of NfL. The levels of CSF NfL were significantly higher in early onset Alzheimer’s disease compared to controls (PMID:17290105)
• The stationary neurofilament (NF) network in axons is a key determinant of half-life and transport rate of endogenous NF-L proteins. (PMID:17475803)
• results argue against an obvious genotype-phenotype correlation regarding Charcot-Marie-Tooth disease onset, degree of muscle weakness, and nerve conduction slowing caused by NEFL mutations (PMID:17620486)
• In conclusion, CSF NF-L levels may provide both diagnostic and prognostic information, particularly in SOD1 wt ALS. (PMID:17903209)
• CSF NFL may serve as a useful marker in monitoring CNS injury in HIV-1 infection and in evaluating CNS efficacy of antiretroviral therapy. (PMID:17923616)
• Auditory nerve involvement in the presence of normal cochlear outer hair cell activity is asymptomatic in one of two families with CMT disorder with different point mutations(Pro22Ser and Glu397Lys) of the NF-L gene. (PMID:18023247)
• NEFL Pro22Arg mutation is associated with Charcot-Marie-Tooth disease type 1 (PMID:18758688)
• This protein has been found differentially expressed in the temporal lobe from patients with schizophrenia. (PMID:19034380)
• This protein has been found differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19110265)
• alanine at position 148 is essentially required for NF-L self-assembly leading to subsequent filament formation in neuronal cells (PMID:19123978)
• Nonsense NEFL mutations probably cause a recessive phenotype, in contrast to missense mutations, which cause a dominant phenotype. (PMID:19158810)
• Our results emphasize the complexity of genotype-phenotype correlations in CMT and underline the possible importance of host factors and gene interactions in the development of clinical phenotypes. (PMID:19286384)
• While RGNEF and NFL mRNA interact directly in vitro, interestingly they only appear to interact in amyotrophic lateral sclerosis lysates and not in controls (PMID:19488899)
• cerebrospinal fluid NFL is not a molecular marker of axonal damage for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) probably due to the slow progression of this disease. (PMID:19678766)
• novel mutation in vocal cord paralysis (PMID:19950375)
• These results confirm that neurofilaments are the main determinant of axonal caliber and conduction velocity. (PMID:20039262)
• Data suggest that the neurofilament light level could be used as a prognostic marker in early relapsing-remitting multiple sclerosis. (PMID:20086018)
• the importance of alpha-internexin and NF-L in regulating the conformations of NF-M and NF-H (PMID:20213320)
• This protein has been found differentially expressed in the anterior cingulate cortex from patients with schizophrenia (PMID:20381070)
• Normal cerebrospinal fluid levels of NFL at 12 months post-operatively and beyond suggest the absence of any long-term neuronal damage caused by long-term deep brain stimulation treatment in Parkinson’s disease. (PMID:21039366)
• NFL levels were not significantly increased in multiple sclerosis patients compared with controls and had no relationship to disability or progression (PMID:21197541)
• Cerebrospinal fluid biomarker NF-L in white matter lesions differentiates patients with subcortical vascular disease from those with Alzheimer’s. (PMID:21860087)
• Subjects with APOE epsilon4 have higher CSF NFL levels than non-epsilon4 carriers, only when they do not carry a short poly-T variant of TOMM40, which is associated with later age of onset of AD. (PMID:21983493)
• Neurofilament light polypeptide (NEFL) was identified as a novel hypermethylated gene associated with resistance to cisplatin-based chemotherapy in cancer of head and neck. (PMID:22246235)
• Identification of gaiting defects combined with previously observed muscle atrophy, reduced axon caliber, and decreased nerve conduction velocity suggests that hNF-L(E397K) mice recapitulate many clinical signs associated with Charcot-Marie-Tooth disease. (PMID:22288874)
• Depressed neurofilament expression associates with apolipoprotein E3/E4 genotype in maturing human fetal neurons exposed to HIV-1. (PMID:22302611)
• NEFL mRNA is ectopically expressed in breast malignancies and could be a potential prognostic factor for early-stage breast cancer patients (PMID:22319610)
• High CSF NFL levels were found in patients with amyotrophic lateral sclerosis ( (PMID:22680408)
• Within 7 days after cardiac arrest, serum NF-L is a valuable marker of long-term poor neurological outcome. (PMID:23287695)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	neflb	ENSDARG00000012426
mus_musculus	Nefl	ENSMUSG00000022055
rattus_norvegicus	Nefl	ENSRNOG00000013658

Paralogs (68): KRT33A (ENSG00000006059), VIM (ENSG00000026025), KRT31 (ENSG00000094796), NEFM (ENSG00000104722), KRT23 (ENSG00000108244), KRT37 (ENSG00000108417), KRT32 (ENSG00000108759), KRT18 (ENSG00000111057), LMNB1 (ENSG00000113368), KRT36 (ENSG00000126337), KRT17 (ENSG00000128422), GFAP (ENSG00000131095), KRT34 (ENSG00000131737), KRT33B (ENSG00000131738), NES (ENSG00000132688), PRPH (ENSG00000135406), KRT85 (ENSG00000135443), KRT7 (ENSG00000135480), KRT71 (ENSG00000139648), INA (ENSG00000148798), LMNTD1 (ENSG00000152936), LMNA (ENSG00000160789), KRT84 (ENSG00000161849), KRT82 (ENSG00000161850), KRT80 (ENSG00000167767), KRT1 (ENSG00000167768), KRT24 (ENSG00000167916), KRT8 (ENSG00000170421), KRT78 (ENSG00000170423), KRT86 (ENSG00000170442), KRT75 (ENSG00000170454), KRT6C (ENSG00000170465), KRT4 (ENSG00000170477), KRT74 (ENSG00000170484), KRT72 (ENSG00000170486), KRT83 (ENSG00000170523), BFSP2 (ENSG00000170819), KRT19 (ENSG00000171345), KRT15 (ENSG00000171346), KRT38 (ENSG00000171360)

Protein

Protein identifiers

Neurofilament light polypeptide — P07196 (reviewed: P07196)

Alternative names: 68 kDa neurofilament protein, Neurofilament triplet L protein

All UniProt accessions (1): P07196

UniProt curated annotations — full annotation on UniProt →

Function. Neurofilaments usually contain three intermediate filament proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of neuronal caliber. May additionally cooperate with the neuronal intermediate filament proteins PRPH and INA to form neuronal filamentous networks.

Subunit / interactions. Forms homodimers (in vitro). Forms heterodimers with NEFH or NEFM; which can further hetero-oligomerize (in vitro). Forms heterodimers with INA (in vitro). Interacts with ARHGEF28. Interacts with TRIM2.

Subcellular location. Cell projection. Axon. Cytoplasm. Cytoskeleton.

Post-translational modifications. O-glycosylated. Phosphorylated in the head and rod regions by the PKC kinase PKN1, leading to the inhibition of polymerization. Ubiquitinated in the presence of TRIM2 and UBE2D1.

Disease relevance. Charcot-Marie-Tooth disease, demyelinating, type 1F (CMT1F) [MIM:607734] A dominant demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. CMT1F is characterized by onset in infancy or childhood (range 1 to 13 years). The disease is caused by variants affecting the gene represented in this entry. Charcot-Marie-Tooth disease, axonal, type 2E (CMT2E) [MIM:607684] A dominant axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. The disease is caused by variants affecting the gene represented in this entry. Charcot-Marie-Tooth disease, dominant intermediate G (CMTDIG) [MIM:617882] An autosomal dominant, intermediate form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Dominant intermediate forms are characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec. CMTDIG is phenotypically variable. Most affected individuals have onset in the first or second decades of slowly progressive distal motor weakness and atrophy, resulting in gait instability and distal upper limb impairment, as well as distal sensory impairment. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The extra mass and high charge density that distinguish the neurofilament proteins from all other intermediate filament proteins are due to the tailpiece extensions. This region may form a charged scaffolding structure suitable for interaction with other neuronal components or ions.

Miscellaneous. NF-L is the most abundant of the three neurofilament proteins and, like the other nonepithelial intermediate filament proteins, it can form homomeric 10-nm filaments.

Similarity. Belongs to the intermediate filament family.

RefSeq proteins (1): NP_006149* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006821	Intermed_filament_DNA-bd	Domain
IPR018039	IF_conserved	Conserved_site
IPR039008	IF_rod_dom	Domain
IPR050405	Intermediate_filament	Family

Pfam: PF00038, PF04732

UniProt features (56 total): sequence variant 17, region of interest 13, modified residue 11, sequence conflict 8, compositionally biased region 2, glycosylation site 2, initiator methionine 1, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07196-F1	73.66	0.45

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (11): 2, 23, 23, 30, 43, 56, 67, 103, 472, 502, 520

Glycosylation sites (2): 21, 27

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-438066	Unblocking of NMDA receptors, glutamate binding and activation
R-HSA-442982	Ras activation upon Ca2+ influx through NMDA receptor
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-9609736	Assembly and cell surface presentation of NMDA receptors
R-HSA-9617324	Negative regulation of NMDA receptor-mediated neuronal transmission
R-HSA-9620244	Long-term potentiation

MSigDB gene sets: 514 (showing top): GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, BENPORATH_ES_WITH_H3K27ME3, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, GOBP_AXO_DENDRITIC_TRANSPORT, LUCAS_HNF4A_TARGETS_DN, GOBP_INTERMEDIATE_FILAMENT_ORGANIZATION, PEREZ_TP63_TARGETS, GOBP_RESPONSE_TO_CORTICOSTEROID, JOHANSSON_GLIOMAGENESIS_BY_PDGFB_DN, GOBP_REGENERATION, GOBP_NEUROGENESIS, GOBP_RESPONSE_TO_AXON_INJURY, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT

GO Biological Process (30): microtubule cytoskeleton organization (GO:0000226), axonogenesis (GO:0007409), anterograde axonal transport (GO:0008089), retrograde axonal transport (GO:0008090), response to toxic substance (GO:0009636), peripheral nervous system axon regeneration (GO:0014012), axonal transport of mitochondrion (GO:0019896), spinal cord development (GO:0021510), hippocampus development (GO:0021766), cerebral cortex development (GO:0021987), regulation of axon diameter (GO:0031133), neurofilament bundle assembly (GO:0033693), locomotion (GO:0040011), response to peptide hormone (GO:0043434), intermediate filament polymerization or depolymerization (GO:0045105), intermediate filament organization (GO:0045109), positive regulation of axonogenesis (GO:0050772), neuromuscular process controlling balance (GO:0050885), protein polymerization (GO:0051258), response to corticosterone (GO:0051412), neurofilament cytoskeleton organization (GO:0060052), regulation of synapse maturation (GO:0090128), motor neuron apoptotic process (GO:0097049), postsynaptic modulation of chemical synaptic transmission (GO:0099170), response to sodium arsenite (GO:1903935), response to acrylamide (GO:1903937), negative regulation of motor neuron apoptotic process (GO:2000672), intermediate filament bundle assembly (GO:0045110), neuron projection morphogenesis (GO:0048812), postsynaptic intermediate filament cytoskeleton organization (GO:0099185)

GO Molecular Function (9): structural constituent of cytoskeleton (GO:0005200), tubulin binding (GO:0015631), protein domain specific binding (GO:0019904), protein-macromolecule adaptor activity (GO:0030674), identical protein binding (GO:0042802), phospholipase binding (GO:0043274), protein-containing complex binding (GO:0044877), structural constituent of postsynaptic intermediate filament cytoskeleton (GO:0099184), protein binding (GO:0005515)

GO Cellular Component (16): cytoplasm (GO:0005737), cytosol (GO:0005829), intermediate filament (GO:0005882), neurofilament (GO:0005883), axon (GO:0030424), growth cone (GO:0030426), neuromuscular junction (GO:0031594), Schaffer collateral - CA1 synapse (GO:0098685), cholinergic synapse (GO:0098981), postsynaptic intermediate filament cytoskeleton (GO:0099160), presynaptic intermediate filament cytoskeleton (GO:0099182), axon cytoplasm (GO:1904115), cytoskeleton (GO:0005856), cell projection (GO:0042995), neuron projection (GO:0043005), intermediate filament cytoskeleton (GO:0045111)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Activation of NMDA receptors and postsynaptic events	3
CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling	1
MAPK1/MAPK3 signaling	1
Post NMDA receptor activation events	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
axonal transport	3
axon cytoplasm	3
anatomical structure development	3
protein binding	3
cellular anatomical structure	3
intermediate filament cytoskeleton	3
synapse	3
cytoskeleton organization	2
pallium development	2
regulation of axonogenesis	2
intermediate filament cytoskeleton organization	2
cytoskeleton	2
binding	2
cytoplasm	2
microtubule-based process	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
response to chemical	1
axon regeneration	1
mitochondrion transport along microtubule	1
central nervous system development	1
limbic system development	1
regulation of cell projection size	1
intermediate filament bundle assembly	1
biological_process	1
response to hormone	1
response to nitrogen compound	1
response to oxygen-containing compound	1
protein-containing complex organization	1
supramolecular fiber organization	1
axonogenesis	1
positive regulation of cell projection organization	1
positive regulation of neurogenesis	1
musculoskeletal movement	1
neuromuscular process	1
protein-containing complex assembly	1
response to glucocorticoid	1
response to mineralocorticoid	1
response to alcohol	1

Protein interactions and networks

STRING

4004 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NEFL	NEFH	P12036	989
NEFL	NEFM	P07197	988
NEFL	INA	Q16352	983
NEFL	MTMR2	Q13614	873
NEFL	MYO5A	Q9Y4I1	823
NEFL	TARDBP	Q13148	781
NEFL	SOD1	P00441	776
NEFL	APP	P05067	765
NEFL	NRGN	Q92686	763
NEFL	MAPT	P10636	761
NEFL	RNMT	O43148	748
NEFL	MAP2	P11137	747
NEFL	GRIN1	P35437	743
NEFL	MBP	P02686	732
NEFL	SNAP25	P13795	730

IntAct

434 interactions, top by confidence:

A	B	Type	Score
NEFL	GFAP	psi-mi:“MI:0915”(physical association)	0.850
GFAP	NEFL	psi-mi:“MI:0915”(physical association)	0.850
VIM	NEFL	psi-mi:“MI:0914”(association)	0.840
NEFL	DES	psi-mi:“MI:0915”(physical association)	0.830
NEFM	NEFL	psi-mi:“MI:0914”(association)	0.800
NEFL	NEFM	psi-mi:“MI:0915”(physical association)	0.800
NEFL	SKIL	psi-mi:“MI:0915”(physical association)	0.720
SKIL	NEFL	psi-mi:“MI:0915”(physical association)	0.720
NDN	NEFL	psi-mi:“MI:0915”(physical association)	0.670
S100P	NEFL	psi-mi:“MI:0915”(physical association)	0.670
SYNC	NEFL	psi-mi:“MI:0915”(physical association)	0.670
NEFL	PPP1R18	psi-mi:“MI:0915”(physical association)	0.560
PPP1R18	NEFL	psi-mi:“MI:0915”(physical association)	0.560
NEFL	KIFC3	psi-mi:“MI:0915”(physical association)	0.560
NEFL	CEP57L1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (206): NEFL (Two-hybrid), NEFL (Two-hybrid), NEFL (Two-hybrid), USP2 (Two-hybrid), PDE4DIP (Two-hybrid), PPP1R16B (Two-hybrid), NME7 (Two-hybrid), TEX11 (Two-hybrid), ENKD1 (Two-hybrid), TXLNB (Two-hybrid), PPP1R18 (Two-hybrid), NEFL (Affinity Capture-MS), NEFL (Affinity Capture-MS), NEFL (Affinity Capture-MS), NEFL (Affinity Capture-MS)

ESM2 similar proteins: A0A8C0N8E3, B4F721, O62654, P02540, P02541, P02542, P02543, P02544, P02547, P02548, P03995, P07196, P08551, P08552, P08670, P09654, P14136, P16053, P17661, P19527, P20152, P23239, P23565, P24789, P24790, P31000, P31001, P31393, P35616, P35617, P46660, P47819, P48616, P48670, P48673, P48674, P48675, P48676, P84198, Q02916

Diamond homologs: A0A125S9M6, A0JND2, A4FUZ0, A5A6M8, A6NCN2, A7YWK3, O43790, P02542, P02545, P02547, P02548, P04104, P04260, P04261, P04262, P04263, P07196, P07744, P08551, P08928, P09010, P10999, P12035, P12036, P13647, P13648, P15241, P16884, P19013, P19246, P19527, P21619, P21910, P25691, P35908, P48671, P48672, P48678, P48679, P78385

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
NEFL	up-regulates	“Neurofilament bundle assembly”
YWHAB	“down-regulates activity”	NEFL	binding
YWHAZ	“down-regulates activity”	NEFL	binding
YWHAE	“down-regulates activity”	NEFL	binding
YWHAQ	“down-regulates activity”	NEFL	binding
YWHAG	“down-regulates activity”	NEFL	binding
PRKACA	“down-regulates activity”	NEFL	phosphorylation
NEFL	“form complex”	“Neurofilament L/M”	binding
NEFL	“form complex”	“Neurofilament L/H”	binding
14-3-3	“down-regulates activity”	NEFL	binding
TRIM2	“down-regulates quantity by destabilization”	NEFL	ubiquitination
OPTN	“up-regulates quantity by expression”	NEFL	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 121 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
intermediate filament organization	7	16.2×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

666 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	30
Likely pathogenic	10
Uncertain significance	393
Likely benign	146
Benign	18

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1215368	NM_006158.5(NEFL):c.417C>G (p.Tyr139Ter)	Pathogenic
14028	NM_006158.5(NEFL):c.995A>C (p.Gln332Pro)	Pathogenic
14030	NM_006158.5(NEFL):c.22_23delinsAG (p.Pro8Arg)	Pathogenic
14033	NM_006158.5(NEFL):c.281T>C (p.Leu94Pro)	Pathogenic
14034	NM_006158.5(NEFL):c.418G>T (p.Glu140Ter)	Pathogenic
1437655	NM_006158.5(NEFL):c.795C>G (p.Tyr265Ter)	Pathogenic
1685968	NM_006158.5(NEFL):c.506dup (p.Thr170fs)	Pathogenic
1685969	NM_006158.5(NEFL):c.54C>G (p.Tyr18Ter)	Pathogenic
192322	NM_006158.5(NEFL):c.1261C>T (p.Arg421Ter)	Pathogenic
1928219	NM_006158.5(NEFL):c.799_803del (p.Lys267fs)	Pathogenic
1973539	NM_006158.5(NEFL):c.832del (p.Glu278fs)	Pathogenic
1984363	NM_006158.4(NEFL):c.1414=	Pathogenic
2090590	NM_006158.5(NEFL):c.1272del (p.Ala423_Tyr424insTer)	Pathogenic
2683878	NM_006158.5(NEFL):c.760del (p.Leu254fs)	Pathogenic
2838458	NM_006158.5(NEFL):c.1240dup (p.Gln414fs)	Pathogenic
29803	NM_006158.5(NEFL):c.628G>T (p.Glu210Ter)	Pathogenic
3022773	NM_006158.5(NEFL):c.865_871del (p.Glu289fs)	Pathogenic
3368912	NM_006158.5(NEFL):c.836G>A (p.Trp279Ter)	Pathogenic
3376740	NM_006158.5(NEFL):c.1357G>T (p.Glu453Ter)	Pathogenic
3639517	NM_006158.5(NEFL):c.171C>G (p.Tyr57Ter)	Pathogenic
3647897	NM_006158.5(NEFL):c.720C>G (p.Tyr240Ter)	Pathogenic
369981	NM_006158.5(NEFL):c.487G>T (p.Glu163Ter)	Pathogenic
3708693	NM_006158.5(NEFL):c.417C>A (p.Tyr139Ter)	Pathogenic
3730542	NM_006158.5(NEFL):c.223C>T (p.Gln75Ter)	Pathogenic
66671	NM_006158.5(NEFL):c.1186G>A (p.Glu396Lys)	Pathogenic
66687	NM_006158.5(NEFL):c.23C>A (p.Pro8Gln)	Pathogenic
66690	NM_006158.5(NEFL):c.268G>A (p.Glu90Lys)	Pathogenic
66698	NM_006158.5(NEFL):c.803T>C (p.Leu268Pro)	Pathogenic
852797	NM_006158.5(NEFL):c.32C>A (p.Ser11Ter)	Pathogenic
916802	NM_006158.5(NEFL):c.1039_1040del (p.Met347fs)	Pathogenic

SpliceAI

317 predictions. Top by Δscore:

Variant	Effect	Δscore
8:24952950:CAG:C	acceptor_gain	1.0000
8:24952953:C:A	acceptor_loss	1.0000
8:24952953:C:CC	acceptor_gain	1.0000
8:24952954:T:C	acceptor_gain	1.0000
8:24952955:T:C	acceptor_gain	1.0000
8:24952955:T:TC	acceptor_gain	1.0000
8:24952959:CA:C	acceptor_gain	1.0000
8:24952960:A:AC	acceptor_gain	1.0000
8:24952960:A:C	acceptor_gain	1.0000
8:24952960:A:T	acceptor_gain	1.0000
8:24952971:A:C	acceptor_gain	1.0000
8:24953473:TACCT:T	donor_loss	1.0000
8:24953474:A:AG	donor_loss	1.0000
8:24953475:C:G	donor_loss	1.0000
8:24953475:CCTT:C	donor_gain	1.0000
8:24953481:T:TA	donor_gain	1.0000
8:24953793:TTC:T	acceptor_gain	1.0000
8:24953796:C:CC	acceptor_gain	1.0000
8:24954302:TGTC:T	acceptor_gain	1.0000
8:24954303:GTC:G	acceptor_gain	1.0000
8:24954304:TC:T	acceptor_gain	1.0000
8:24954305:CC:C	acceptor_gain	1.0000
8:24954306:C:CC	acceptor_gain	1.0000
8:24954306:C:G	acceptor_loss	1.0000
8:24954307:T:A	acceptor_loss	1.0000
8:24954310:T:C	acceptor_gain	1.0000
8:24954310:T:TC	acceptor_gain	1.0000
8:24954317:C:CT	acceptor_gain	1.0000
8:24954318:A:T	acceptor_gain	1.0000
8:24955469:CACC:C	donor_loss	1.0000

AlphaMissense

3575 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:24953782:C:G	G395R	1.000
8:24953786:C:A	L393F	1.000
8:24953786:C:G	L393F	1.000
8:24953787:A:C	L393W	1.000
8:24953787:A:G	L393S	1.000
8:24953790:A:G	L392P	1.000
8:24953790:A:T	L392H	1.000
8:24953795:C:A	R390S	1.000
8:24953795:C:G	R390S	1.000
8:24954181:C:A	R390M	1.000
8:24954181:C:G	R390T	1.000
8:24954185:A:C	Y389D	1.000
8:24954185:A:G	Y389H	1.000
8:24954187:G:T	A388D	1.000
8:24954188:C:G	A388P	1.000
8:24954191:C:G	A387P	1.000
8:24954193:A:C	I386S	1.000
8:24954193:A:G	I386T	1.000
8:24954193:A:T	I386N	1.000
8:24954194:T:A	I386F	1.000
8:24954195:C:A	E385D	1.000
8:24954195:C:G	E385D	1.000
8:24954196:T:A	E385V	1.000
8:24954196:T:C	E385G	1.000
8:24954196:T:G	E385A	1.000
8:24954197:C:T	E385K	1.000
8:24954202:T:A	D383V	1.000
8:24954202:T:C	D383G	1.000
8:24954202:T:G	D383A	1.000
8:24954203:C:A	D383Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000373315 (8:24951944 G>T), RS1000715649 (8:24950667 C>T), RS1000924050 (8:24956975 G>A,T), RS1002264026 (8:24950994 A>G,T), RS1002301682 (8:24954559 T>C), RS1002415567 (8:24957447 A>G), RS1002489268 (8:24957765 T>C), RS1002596751 (8:24950760 G>A), RS1003191200 (8:24952141 T>A), RS1003418276 (8:24951149 G>C), RS1003675992 (8:24952421 A>G), RS1004268488 (8:24954889 TAGA>T), RS1004301107 (8:24955314 T>A), RS1004434510 (8:24954214 T>A,C,G), RS1004839739 (8:24953079 T>A)

Disease associations

OMIM: gene MIM:162280 | disease phenotypes: MIM:607684, MIM:617882, MIM:607734, MIM:118220, MIM:601098, MIM:618400, MIM:609129, MIM:182960

GenCC curated gene-disease

Disease	Classification	Inheritance
Charcot-Marie-Tooth disease	Definitive	Autosomal dominant
Charcot-Marie-Tooth disease type 2	Definitive	Autosomal recessive
Charcot-Marie-Tooth disease type 1F	Strong	Autosomal dominant
Charcot-Marie-Tooth disease type 2B5	Supportive	Autosomal recessive
Charcot-Marie-Tooth disease type 2E	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Charcot-Marie-Tooth disease type 2	Definitive	AR
Charcot-Marie-Tooth disease	Definitive	AD

Mondo (15): Charcot-Marie-Tooth disease type 2E (MONDO:0011894), Charcot-Marie-Tooth disease, dominant intermediate G (MONDO:0036484), Charcot-Marie-Tooth disease type 1F (MONDO:0011902), Charcot-Marie-Tooth disease (MONDO:0015626), peripheral neuropathy (MONDO:0005244), Charcot-Marie-Tooth disease type 1C (MONDO:0010995), Charcot-Marie-Tooth disease, axonal, type 2EE (MONDO:0032728), auditory neuropathy (MONDO:0021944), sensorineural hearing loss disorder (MONDO:0020678), hereditary motor neuron disease (MONDO:0024257), distal hereditary motor neuropathy (MONDO:0018894), neuronopathy, distal hereditary motor, autosomal dominant (MONDO:0015362), Charcot-Marie-Tooth disease type 1 (MONDO:0019011), Charcot-Marie-Tooth disease type 2 (MONDO:0018993), Charcot-Marie-Tooth disease type 2B5 (MONDO:0016454)

Orphanet (8): Autosomal dominant Charcot-Marie-Tooth disease type 2E (Orphanet:99939), Charcot-Marie-Tooth disease type 1F (Orphanet:101085), Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy (Orphanet:166), Charcot-Marie-Tooth disease type 1C (Orphanet:101083), Genetic motor neuron disease (Orphanet:98505), Distal hereditary motor neuropathy (Orphanet:53739), Autosomal dominant distal hereditary motor neuropathy (Orphanet:140465), Charcot-Marie-Tooth disease type 1 (Orphanet:65753)

HPO phenotypes

106 total (30 of 106 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000020	Urinary incontinence
HP:0000218	High palate
HP:0000365	Hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000508	Ptosis
HP:0000609	Optic nerve hypoplasia
HP:0000639	Nystagmus
HP:0000762	Decreased nerve conduction velocity
HP:0001155	Abnormality of the hand
HP:0001171	Split hand
HP:0001178	Ulnar claw
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001270	Motor delay
HP:0001284	Areflexia
HP:0001288	Gait disturbance
HP:0001337	Tremor
HP:0001371	Flexion contracture
HP:0001760	Abnormal foot morphology
HP:0001761	Pes cavus
HP:0001765	Hammertoe
HP:0001884	Talipes calcaneovalgus
HP:0002015	Dysphagia
HP:0002066	Gait ataxia

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002363_3	Response to anti-retroviral therapy (ddI/d4T) in HIV-1 infection (Grade 3 peripheral neuropathy)	6.000000e-06
GCST002365_1	Response to anti-retroviral therapy (ddI/d4T) in HIV-1 infection (Grade 2 peripheral neuropathy)	5.000000e-06
GCST004708_10	Fear of minor pain	1.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0000180	HIV-1 infection
EFO:0008340	fear of minor pain measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D002607	Charcot-Marie-Tooth Disease	C10.500.300.200; C10.574.500.495.200; C10.668.829.800.300.200; C16.131.666.300.200; C16.320.400.375.200
C538268	Auditory neuropathy (supp.)
C537984	Charcot-Marie-Tooth disease, Type 1C (supp.)
C537987	Charcot-Marie-Tooth disease, Type 1F (supp.)
C537994	Charcot-Marie-Tooth disease, Type 2E (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

91 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	8
sodium arsenite	affects methylation, affects expression, decreases expression, increases expression, affects acetylation	5
Tretinoin	increases expression, decreases expression, affects cotreatment	4
trichostatin A	increases expression, affects cotreatment	3
Benzo(a)pyrene	increases methylation, affects methylation, decreases methylation, increases expression	3
Doxorubicin	increases expression	3
methylmercuric chloride	increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression, increases expression	2
Alitretinoin	affects expression, decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Rotenone	increases expression, decreases expression	2
Cadmium Chloride	increases abundance, increases expression	2
FR900359	increases phosphorylation	1
4-oxoretinoic acid	decreases expression	1
methyleugenol	increases expression	1
uranyl acetate	affects expression	1
propionaldehyde	increases expression	1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	affects cotreatment, increases expression	1
arsenite	increases methylation	1
cypermethrin	decreases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	increases expression	1
tri-o-cresyl phosphate	decreases expression, decreases reaction	1
3-methyladenine	decreases expression, decreases reaction	1
leupeptin	decreases reaction, increases degradation	1
aluminum sulfate	decreases expression	1
beta-methylcholine	affects expression	1

Cellosaurus cell lines

4 cell lines: 3 induced pluripotent stem cell, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D8R5	Ubigene HCT 116 NEFL KO	Cancer cell line	Male
CVCL_JX01	NYSCF-AG0010-01-MR	Induced pluripotent stem cell	Male
CVCL_JX07	NYSCF-AG0016-01-MR	Induced pluripotent stem cell	Female
CVCL_JX09	NYSCF-AG0018-01-MR	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

299 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00380965	PHASE4	COMPLETED	Evaluation of the Efficacy of Cesamet™ for the Treatment of Pain in Patients With Chemotherapy-Induced Neuropathy
NCT00487981	PHASE4	TERMINATED	Spinal Cord Stimulation for Painful Diabetic Neuropathy
NCT00904202	PHASE4	COMPLETED	A Study Of Lidocaine Patch 5% Alone, Gabapentin Alone, And Lidocaine Patch 5% And Gabapentin In Combination For The Relief Of Pain In Patients With Diverse Peripheral Neuropathic Pain Conditions
NCT01192113	PHASE4	COMPLETED	Safety and Efficacy of Mecobalamin Injection in Peripheral Neuropathies Patients (Study JGAZSY091109)
NCT01373983	PHASE4	COMPLETED	Intrathecal Bolus Doses of Ziconotide
NCT01458015	PHASE4	TERMINATED	Tapentadol Versus Oxycodone - a Mechanism-based Treatment Approach in Neuropathic Pain
NCT02074267	PHASE4	COMPLETED	Clinical Study for Assessment of the Efficacy of Gabapentin (Carbatin and Neurontin) in Patients With Neuropathy Pain
NCT02372149	PHASE4	UNKNOWN	IVIg for Demyelination in Diabetes Mellitus
NCT02670161	PHASE4	ENROLLING_BY_INVITATION	Quality Improvement and Practice Based Research in Neurology Using the EMR
NCT07022938	PHASE4	COMPLETED	Nutritional Supplement for Treating Chemotherapy Induced Neuropathy
NCT07025005	PHASE4	RECRUITING	Fenofibrate Role in the Prophylaxis From Peripheral Neuropathy Induced by Bortezomib, Lenalidomide and Dexamethasone (VRd) Protocol in the Treatment of Patients With Multiple Myeloma (MM)
NCT04762758	PHASE3	UNKNOWN	Phase III Trial Assessing the Efficacy and Safety of PXT3003 in CMT1A Patients
NCT00058071	PHASE3	COMPLETED	Amifostine in Treating Peripheral Neuropathy in Patients Who Have Received Chemotherapy for Cancer
NCT00125268	PHASE3	TERMINATED	Near Infrared Light for the Treatment of Painful Peripheral Neuropathy
NCT00195013	PHASE3	COMPLETED	Randomized Placebo-Controlled Trial of Glutamine for Breast Cancer Patients With Peripheral Neuropathy
NCT00232141	PHASE3	COMPLETED	Study of Pregabalin Versus Placebo in the Treatment of Nerve Pain Associated With HIV Neuropathy
NCT00264875	PHASE3	COMPLETED	Open Label Safety And Efficacy Study Of Pregabalin In Subjects With Nerve Pain Asociated With Human Immunodeficiency Virus (HIV) Neuropathy
NCT00369564	PHASE3	COMPLETED	Glutamic Acid in Reducing Nerve Damage Caused by Vincristine in Young Patients With Cancer
NCT00471445	PHASE3	COMPLETED	Topical Amitriptyline and Ketamine Cream in Treating Peripheral Neuropathy Caused by Chemotherapy in Cancer Patients
NCT00489411	PHASE3	COMPLETED	Duloxetine in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer
NCT00710554	PHASE3	COMPLETED	A Study of Sativex® for Pain Relief of Peripheral Neuropathic Pain, Associated With Allodynia
NCT00711880	PHASE3	COMPLETED	A Study of Sativex® for Relief of Peripheral Neuropathic Pain Associated With Allodynia.
NCT00713323	PHASE3	COMPLETED	A Study to Compare the Safety and Tolerability of Sativex® in Patients With Neuropathic Pain.
NCT00713817	PHASE3	COMPLETED	A Study to Determine the Maintenance of Effect After Long-term Treatment of Sativex® in Subjects With Neuropathic Pain
NCT00775645	PHASE3	COMPLETED	S0715: Acetyl-L-Carnitine in Preventing Neuropathy in Women With Stage I, II, or IIIA Breast Cancer Undergoing Chemo
NCT00872352	PHASE3	UNKNOWN	Evaluation of Bortezomib Induced Peripheral Neuropathy of Multiple Myeloma (MM) Patients
NCT00998738	PHASE3	TERMINATED	Calcium and Magnesium in Preventing Peripheral Neuropathy Caused by Ixabepilone in Patients With Breast Cancer
NCT01049217	PHASE3	TERMINATED	Pregabalin Versus Placebo In The Treatment Of Neuropathic Pain Associated With HIV Neuropathy
NCT01099449	PHASE3	COMPLETED	Calcium Gluconate and Magnesium Sulfate in Preventing Neurotoxicity in Patients With Colon Cancer or Rectal Cancer Receiving Oxaliplatin-Based Combination Chemotherapy
NCT01288937	PHASE3	TERMINATED	A Placebo Controlled, Randomized, Double Blind Trial of Milnacipran for the Treatment of Idiopathic Neuropathy Pain
NCT01492920	PHASE3	WITHDRAWN	Acetyl-L-Carnitine Hydrochloride in Preventing Peripheral Neuropathy in Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer Undergoing Chemotherapy
NCT01775449	PHASE3	COMPLETED	Prevention of Oxaliplatin-induced Neuropathic Pain by a Specific Diet
NCT02024191	PHASE3	UNKNOWN	The Role of Glutamine for Preventing Oxaliplatin-Induced Peripheral Neuropathy
NCT02217267	PHASE3	COMPLETED	Long Term Outcome After Serial Lidocaine Infusion in Peripheral Neuropathic Pain
NCT02294149	PHASE3	UNKNOWN	Vit D3 and Omega 3 in Chemo Induced Neuropathy
NCT02311907	PHASE3	COMPLETED	Glutathione in Preventing Peripheral Neuropathy Caused by Paclitaxel and Carboplatin in Patients With Ovarian Cancer, Fallopian Tube Cancer, and/or Primary Peritoneal Cancer
NCT06071936	PHASE3	UNKNOWN	Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Traumatic or Post-operative Peripheral Neuropathy
NCT06071975	PHASE3	UNKNOWN	Long Term Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Diabetic Polyneuropathy
NCT06071988	PHASE3	UNKNOWN	Long Term Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Traumatic or Post-operative Peripheral Neuropathy
NCT06072573	PHASE3	UNKNOWN	Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Diabetic Polyneuropathy